Preliminary studies have shown that food injected into a supernumery transplanted stomach produces an immediate compensatory reduction in food intake. Other studies with two-way intestines-crossed rats established that food absorbed from a twelve-inch intestinal segment does not produce satiety. Both studies together imply that a hormone arising in the stomach, upper duodenum or lower jejunum inhibits food intake. The site of hormone release and its mode of action can be determined by clamping the pyloric sphincter or the artery leading to the transplant. The possibility that cholecystokinin reduces food intake will be investigated in normal rats by intravenous injection and in intestines-crossed rats by bioassay. The long-term feeding behavior and weight regulation of one-way and two-way intestines-crossed rats is strikingly different. Two-way intestines-crossed rats that lose nutrients from the stomach do not increase feeding behavior for 10 days and lose substantial amounts of weight. One-way rat pairs maintain body weight by changing food intake in 3-5 days. One rat eats four times as much as its partner and has less body fat and a smaller liver. The considerable differences in these two types of rat pairs are investigated in several experiments. The importance of intestinal length in inhibiting food intake is investigated by transplanting intestines to increase length or resecting to decrease length. The importance of jejunal or ileal signals for reducing feeding are determined by crossing this lower intestinal segment. The one-way intestines-crossed experiment suggests that the amount of body fat may regulate food intake. This possibility is investigated by transplanting fat. The proposed experiment will establish whether total fat mass is regulated by a chalone, the nutrients released in fat metabolism or a genetic mechanism controlling cell number and size. Changes in fatty acid composition and cell size will be determined when fat is transplanted into rats with VMH or LH lesions. Finally, the relationship between extensive denervation of fat and obesity will be examined.